POS0115 DAPIROLIZUMAB PEGOL EFFICACY BY SUBGROUPS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: A POST HOC ANALYSIS OF PHASE 2 CLINICAL TRIAL DATA
Authors: A. Askanase, C. Stach, C. Brittain, G. Stojan, R. Furie
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic lupus erythematosus (SLE) clinical trials are challenged by high placebo response rates. Subgroup analyses of historic SLE clinical trial data have identified acute flares with normal complement levels as potential predictors of high placebo response. <h3>Objectives</h3> To assess the treatment effect of dapirolizumab pegol (DZP; a polyethylene glycol conjugated antigen-binding fragment lacking a functional Fc domain, which inhibits the CD40–CD40 ligand interaction) in patients from the phase 2b trial in SLE,<sup>[1]</sup> who fulfilled one or both of the characteristics identified as potential predictors of placebo response. <h3>Methods</h3> Post hoc analyses were performed on data from a phase 2b trial (NCT02804763), in which patients received placebo or DZP (6/24/45 mg/kg), alongside standard of care (SOC) for 24 weeks.<sup>[1]</sup> Efficacy was compared between two subgroups: (<b>1</b>) acute flare with low C3/C4 or persistent disease activity, vs (<b>2</b>) acute flare without low C3/C4. In the subgroup analyses, disease activity at screening was defined using British Isles Lupus Assessment Group (BILAG) 2004 item level scores either as acute flare (worsening/new symptoms) or persistent (symptoms rated as the same) based on the past 4 weeks compared with the 4 weeks prior to those, and low C3/C4 was defined as below the lower limit of normal at screening. Outcomes assessed were BILAG-based Composite Lupus Assessment (BICLA) response, SLE Responder Index-4 (SRI-4) response, and change from baseline in Physician's Global Assessment (PGA) at Week 24. Binary outcomes were analysed using logistic regression (p-values reported for odds ratio vs acute flare without low C3/C4), and continuous outcomes were analysed using mixed models with repeat measures (p-values reported for difference vs acute flare without low C3/C4). <h3>Results</h3> <b>Figure 1a</b> and <b>1b</b> show BICLA responses in the subgroups over time; similar patterns were seen for the other outcomes. At Week 24, higher BICLA response rates were achieved across all treatment arms in the acute flare without low C3/C4 subgroup compared with the other subgroup (<b>Figure 1c</b>). This pattern was particularly evident in patients receiving SOC plus placebo, where there was a significant 3-fold difference in BICLA response rates between the subgroups (80.0% vs 24.2%; p=0.005). Patients who received SOC plus placebo in the acute flare without low C3/C4 subgroup also achieved numerically higher SRI-4 response rates than the acute flare with low C3/C4 or persistent disease activity subgroup. A similar pattern was observed for patients who received SOC plus 6 mg/kg DZP; however, comparable SRI-4 response rates were observed between subgroups in patients who received SOC plus 24/45 mg/kg DZP (<b>Figure 1d</b>). At Week 24, greater changes from baseline in PGA were achieved in patients receiving SOC plus placebo in the acute flare without low C3/C4 subgroup than in the acute flare with low C3/C4 or persistent disease activity subgroup (least squares mean: −42.0 vs −24.9; p=0.0268). Comparable changes in PGA were seen between subgroups for patients receiving SOC plus DZP (<b>Figure 1e</b>). <h3>Conclusion</h3> Despite the limited sample size, patients with acute flare with normal complement levels were more likely to achieve responses to SOC plus placebo, diminishing the DZP treatment effect. These data suggest that SLE trial design may need to consider baseline clinical and serologic activity patterns to adequately assess treatment efficacy. <h3>Reference</h3> [1]Furie RA. Rheumatology (Oxford) 2021;60:5397–407. <h3>Acknowledgements</h3> Funded by UCB Pharma and Biogen Inc. Medical writing support provided by Costello Medical and funded by UCB Pharma and Biogen Inc. <h3>Disclosure of Interests</h3> Anca Askanase Consultant of: AbbVie, Amgen, AstraZeneca, Aurinia, BMS, Celgene, Eli Lilly, Idorsia, Janssen, Genentech, GSK, Mallinckrodt, Pfizer and UCB Pharma, Grant/research support from: AstraZeneca, BMS, Eli Lilly, Idorsia, Janssen, Genentech, GSK, Mallinckrodt, Pfizer and UCB Pharma, Christian Stach Shareholder of: UCB Pharma, Employee of: UCB Pharma, Claire Brittain Shareholder of: UCB Pharma, Employee of: UCB Pharma, George Stojan Employee of: UCB Pharma, Richard Furie Consultant of: Biogen Inc. and UCB Pharma, Grant/research support from: Biogen Inc. and UCB Pharma.